[Effects and Mechanism of PARP Inhibitor Olaparib on the Expression of NKG2D Ligands in HL-60 Cells]

To investigate the regulatory effects of Olaparib on natural killer cell activating receptor (NKG2D) ligands expression on human acute myeloid leukemia (AML) cell line HL-60, and to explore the molecular mechanism of Olaparib on HL-60 cells.After HL-60 cells in logarithmic growth phase were treated with Olaparib at different concentrations for different times (24, 48 h), the expression of NKG2D ligand on the surface of HL-60 cells was detected by flow cytometry. Western blot was used to dectect the expression of ERK expression in HL-60 cells. The killing effect of NK cells to HL-60 cells was detected by CFSE/PI method.10 μmol/L Olaparib could upregulate the expression of NKG2D ligand on the surface of HL-60 cell at 24 and 48 hours, while 5 μmol/L Olaparib could induce up-regulation of the expression of ULBP-2 and ULBP-3 at 48 hours. Western blot analysis showed that ERK phosphorylation of HL-60 cells was enhanced after treating with Olaparib. The killing effect of NK cells to HL-60 cells could be enhanced by Olaparib, however, ERK inhibitor could suppress the killing effect of NK cells to HL-60 cells.Olaparib can upregulate NKG2D ligands expression on the surface of HL-60 cells and enhance the cytotoxicity of NK cell to HL-60 cells. The mechanism may be related to Olaparib promoting ERK phosphorylation expression.Olaparib对HL-60细胞NKG2D配体表达的调节作用及相关机制研究.研究Olaparib对人急性髓系白血病细胞株HL-60细胞表面NKG2D配体表达的调节作用, 并初步探索其内在调控机制。.对数生长期的HL-60细胞经不同浓度Olaparib（1.25、2.5、5、10 μmol/L）作用24、48 h后, 采用流式细胞术检测细胞表面NKG2D配体表达情况；Western blot检测HL-60细胞内ERK蛋白表达变化情况；CFSE/PI法检测NK细胞对HL-60细胞的杀伤作用。.10 μmol/L Olaparib作用24和48 h均可上调HL-60细胞表面NKG2D配体的表达, 5 μmol/L Olaparib作用48 h可诱导ULBP-2、ULBP-3表达上调；Western blot检测结果显示, Olaparib处理后的HL-60细胞内ERK磷酸化水平增强。Olaparib可增强NK细胞对HL-60细胞的杀伤作用, 但ERK抑制剂可下调NK细胞对HL-60细胞的杀伤作用。.Olaparib可上调HL-60细胞表面NKG2D配体表达, 增强NK细胞对其的杀伤作用, 其机制可能与Olaparib促进ERK磷酸化表达有关。.